tbuckley/cabot-search huggingface dataset:
Association of Education With Dementia Incidence Stratified by Ethnicity and Nativity in a Cohort of Older Asian American Individuals
Authors: Eleanor Hayes-Larson, Ryo Ikesu, Joseph Fong, Taylor M. Mobley, Gilbert C. Gee, Ron Brookmeyer, Rachel A. Whitmer, Paola Gilsanz, Elizabeth Rose Mayeda
Journal: JAMA Network Open (2023)

Importance High education protects against dementia, but returns on educational attainment may be different across sociodemographic groups owing to various social factors. Asian American individuals are a growing and diverse group, but little research has assessed dementia determinants in this population. Objective To examine the association of education with dementia in a large cohort of Asian American individuals, stratifying by ethnicity and nativity. Design, Setting, and Participants This cohort study used electronic health record (EHR) and survey data from the Research Program on Genes, Environment, and Health and the California Men’s Health Study surveys (2002-2020). Data are from Kaiser Permanente Northern California, an integrated health care delivery system. This study used a volunteer sample who completed the surveys. Participants included Chinese, Filipino, and Japanese individuals who were aged 60 to less than 90 years without a dementia diagnosis in the EHR at the time of the survey (baseline) and who had 2 years of health plan coverage before baseline. Data analysis was performed from December 2021 to December 2022. Exposures The main exposure was educational attainment (college degree or higher vs less than a college degree), and the main stratification variables were Asian ethnicity and nativity (born in the US or born outside the US). Main Outcomes and Measures The primary outcome was incident dementia diagnosis in the EHR. Dementia incidence rates were estimated by ethnicity and nativity, and Cox proportional hazards and Aalen additive hazards models were fitted for the association of college degree or higher vs less than a college degree with time to dementia, adjusting for age (timescale), sex, nativity, and an interaction between nativity and college degree. Results Among 14 749 individuals, the mean (SD) age at baseline was 70.6 (7.3) years, 8174 (55.4%) were female, and 6931 (47.0%) had attained a college degree. Overall, among individuals born in the US, those with a college degree had 12% lower dementia incidence (HR, 0.88; 95% CI, 0.75-1.03) compared with those without at least a college degree, although the confidence interval included the null. The HR for individuals born outside the US was 0.82 (95% CI, 0.72-0.92; P = .46 for the college degree by nativity interaction). The findings were similar across ethnicity and nativity groups except for Japanese individuals born outside the US. Conclusions and Relevance These findings suggest that college degree attainment was associated with lower dementia incidence, with similar associations across nativity. More work is needed to understand determinants of dementia in Asian American individuals and to elucidate mechanisms linking educational attainment and dementia.
Targeting STING Activation by Antigen‐Inspired MnO<sub>2</sub> Nanovaccines Optimizes Tumor Radiotherapy
Authors: Yuan Gu, Subin Lin, Yanxian Wu, Pei Xu, Wen Zhu, Yangyun Wang, Xiaju Cheng, Leshuai W. Zhang, Roland H. Stauber, Yong Wang, Mingyuan Gao
Journal: Advanced Healthcare Materials (2023)

Immune checkpoint blockers therapy can improve the radiotherapy-induced immunosuppression by enhancing interferon secretion, but still suffer from low clinical response rate and potential adverse effects. Mn2+ -mediated activation of interferon gene stimulator (STING) pathway provides an alternative for combination radioimmunotherapy of tumor. However, it is still a challenge for specific delivery of Mn2+ to innate immune cells and targeting activation of STING pathway. Herein, a novel antigen-inspired MnO2 nanovaccine is fabricated as Mn2+ source and functionalized with mannose, enabling it to target innate immune cells to activate the STING pathway. Meanwhile, the release of Mn2+ in the intracellular lysosomes can also be for magnetic resonance imaging to monitor the dynamic distribution of nanovaccines in vivo. The targeting activation of STING pathway can enhance radiotherapy-induced immune responses for inhibiting local and distant tumors, and resisting tumor metastasis. The study proposes an optimized radiotherapy strategy through targeting STING activation of antigen-inspired nanovaccines.
All Patients With a Cerebral Palsy Diagnosis Merit Genomic Sequencing
Authors: Clare van Eyk, Suzanna C. MacLennan, Alastair H. MacLennan
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Parental Nonadherence to Health Policy Recommendations for Prevention of COVID-19 Transmission Among Children
Authors: Andrea Gurmankin Levy, Alistair Thorpe, Laura D. Scherer, Aaron M. Scherer, Jorie M. Butler, Holly Shoemaker, Angela Fagerlin
Journal: JAMA Network Open (2023)

This survey study assesses whether parents had ever engaged in specific misrepresentation and nonadherence behaviors regarding public health measures for preventing COVID-19 transmission among children.
Benefits and Risks of Periconceptional Folic Acid Supplementation
Authors: P. Emanuela Voinescu, Page B. Pennell, Kimford Meador
Journal: JAMA Neurology (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Microenvironment-Driven Dynamic Chromatin Changes in Glioblastoma Recapitulate Early Neural Development at Single-Cell Resolution
Authors: Allison R. Pine, Stefano M. Cirigliano, Richa Singhania, James Nicholson, Bárbara da Silva, Christina S. Leslie, Howard A. Fine
Journal: Cancer Research (2023)

Abstract The tumor microenvironment is necessary for recapitulating the intratumoral heterogeneity and cell state plasticity found in human primary glioblastoma (GBM). Conventional models do not accurately recapitulate the spectrum of GBM cellular states, hindering elucidation of the underlying transcriptional regulation of these states. Using our glioblastoma cerebral organoid model, we profiled the chromatin accessibility of 28,040 single cells in five patient-derived glioma stem cell lines. Integration of paired epigenomes and transcriptomes within the context of tumor-normal host cell interactions was used to probe the gene-regulatory networks underlying individual GBM cellular states in a way not readily possible in other in vitro models. These analyses identified the epigenetic underpinnings of GBM cellular states and characterized dynamic chromatin changes reminiscent of early neural development that underlie GBM cell state transitions. Despite large differences between tumors, a shared cellular compartment made up of neural progenitor-like cells and outer radial glia–like cells was observed. Together, these results shed light on the transcriptional regulation program in GBM and offer novel therapeutic targets across a broad range of genetically heterogenous GBMs. Significance: Single-cell analyses elucidate the chromatin landscape and transcriptional regulation of glioblastoma cellular states and identify a radial glia–like population, providing potential targets to disrupt cell states and improve therapeutic efficacy.
Impact of Ambient Ultrafine Particles on Cause-Specific Mortality in Three German Cities
Authors: Maximilian Schwarz, Alexandra Schneider, Josef Cyrys, Susanne Bastian, Susanne Breitner, Annette Peters
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Exposure to ambient air pollution has been associated with adverse effects on morbidity and mortality. However, the evidence for ultrafine particles (UFPs; 10-100 nm) based on epidemiological studies remains scarce and inconsistent. Objectives: We examined associations between short-term exposures to UFPs and total particle number concentrations (PNCs; 10-800 nm) and cause-specific mortality in three German cities: Dresden, Leipzig, and Augsburg. Methods: We obtained daily counts of natural, cardiovascular, and respiratory mortality between 2010 and 2017. UFPs and PNCs were measured at six sites, and measurements of fine particulate matter (PM2.5; ⩽2.5 μm in aerodynamic diameter) and nitrogen dioxide were collected from routine monitoring. We applied station-specific confounder-adjusted Poisson regression models. We investigated air pollutant effects at aggregated lags (0-1, 2-4, 5-7, and 0-7 d after UFP exposure) and used a novel multilevel meta-analytical method to pool the results. Additionally, we assessed interdependencies between pollutants using two-pollutant models. Measurements and Main Results: For respiratory mortality, we found a delayed increase in relative risk of 4.46% (95% confidence interval, 1.52 to 7.48%) per 3,223-particles/cm3 increment 5-7 days after UFP exposure. Effects for PNCs showed smaller but comparable estimates consistent with the observation that the smallest UFP fractions showed the largest effects. No clear associations were found for cardiovascular or natural mortality. UFP effects were independent of PM2.5 in two-pollutant models. Conclusions: We found delayed effects for respiratory mortality within 1 week after exposure to UFPs and PNCs but no associations for natural or cardiovascular mortality. This finding adds to the evidence on the independent health effects of UFPs.
Patient Characteristics, Outcomes, and Effects of Dapagliflozin According to the Duration of Heart Failure: A Prespecified Analysis of the DELIVER Trial
Authors: Toru Kondo, Karola S. Jering, C. Jan Willem Borleffs, Rudolf A. de Boer, Brian L. Claggett, Akshay S. Desai, Dan Dobreanu, Silvio E. Inzucchi, Adrian F. Hernandez, Stefan P. Janssens, Pardeep S. Jhund, Mikhail N. Kosiborod, Carolyn S.P. Lam, Anna Maria Langkilde, Felipe A. Martinez, Magnus Petersson, Pham Nguyen Vinh, Muthiah Vaduganathan, Scott D. Solomon, John J.V. McMurray
Journal: Circulation (2023)

Background: How patient characteristics and outcomes vary according to the duration of heart failure (HF) is unknown in individuals with mildly reduced or preserved ejection fraction. We compared these, and the efficacy and safety of dapagliflozin, according to the time from diagnosis of HF in a prespecified analysis of the DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure). Methods: HF duration was categorized as ≤6 months, &gt;6 to 12 months, &gt;1 to 2 years, &gt;2 to 5 years, or &gt;5 years. The primary outcome was the composite of worsening HF or cardiovascular death. The effect of treatment was examined by HF duration category. Results: The number of patients in each category was as follows: 1160 (≤6 months), 842 (&gt;6 to 12 months), 995 (&gt;1 to 2 years), 1569 (&gt;2 to 5 years), and 1692 (&gt;5 years). Patients with longer-duration HF were older and had more comorbidities with worse symptoms. The rate of the primary outcome (per 100 person-years) increased with HF duration: ≤6 months, 7.3 (95% CI, 6.3 to 8.4); &gt;6 to 12 months, 7.1 (6.0 to 8.5); &gt;1 to 2 years, 8.4 (7.2 to 9.7); &gt;2 to 5 years, 8.9 (7.9 to 9.9); and &gt;5 years, 10.6 (9.5 to 11.7). Similar trends were seen for other outcomes. The benefit of dapagliflozin was consistent across HF duration category: the hazard ratio for the primary outcome in the ≤6-month group was 0.67 (95% CI, 0.50 to 0.91); &gt;6 to 12 months, 0.78 (0.55 to 1.12); &gt;1 to 2 years, 0.81 (0.60 to 1.09); &gt;2 to 5 years, 0.97 (0.77 to 1.22); and &gt;5 years, 0.78 (0.64 to 0.96; P interaction =0.41). The absolute benefit was greatest in longest-duration HF; the number needed to treat for HF &gt;5 years was 24 versus 32 for ≤6 months. Conclusions: Patients with longer-duration HF were older, had more comorbidities and symptoms, and had higher rates of worsening HF and death. The benefits of dapagliflozin were consistent across HF duration. Even patients with long-standing HF and generally mild symptoms are not stable, and it is not too late for such patients to benefit from a sodium–glucose cotransporter 2 inhibitor. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03619213.
Pulsed Field Ablation for the Treatment of Atrial Fibrillation: PULSED AF Pivotal Trial
Authors: Atul Verma, David E. Haines, Lucas V. Boersma, Nitesh Sood, Andrea Natale, Francis E. Marchlinski, Hugh Calkins, Prashanthan Sanders, Douglas L. Packer, Karl-Heinz Kuck, Gerhard Hindricks, Birce Onal, Jeffrey Cerkvenik, Hiroshi Tada, David B. DeLurgio
Journal: Circulation (2023)

Pulsed field ablation uses electrical pulses to cause nonthermal irreversible electroporation and induce cardiac cell death. Pulsed field ablation may have effectiveness comparable to traditional catheter ablation while preventing thermally mediated complications.The PULSED AF pivotal study (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF) was a prospective, global, multicenter, nonrandomized, paired single-arm study in which patients with paroxysmal (n=150) or persistent (n=150) symptomatic atrial fibrillation (AF) refractory to class I or III antiarrhythmic drugs were treated with pulsed field ablation. All patients were monitored for 1 year using weekly and symptomatic transtelephonic monitoring; 3-, 6-, and 12-month ECGs; and 6- and 12-month 24-hour Holter monitoring. The primary effectiveness end point was freedom from a composite of acute procedural failure, arrhythmia recurrence, or antiarrhythmic escalation through 12 months, excluding a 3-month blanking period to allow recovery from the procedure. The primary safety end point was freedom from a composite of serious procedure- and device-related adverse events. Kaplan-Meier methods were used to evaluate the primary end points.Pulsed field ablation was shown to be effective at 1 year in 66.2% (95% CI, 57.9 to 73.2) of patients with paroxysmal AF and 55.1% (95% CI, 46.7 to 62.7) of patients with persistent AF. The primary safety end point occurred in 1 patient (0.7%; 95% CI, 0.1 to 4.6) in both the paroxysmal and persistent AF cohorts.PULSED AF demonstrated a low rate of primary safety adverse events (0.7%) and provided effectiveness consistent with established ablation technologies using a novel irreversible electroporation energy to treat patients with AF.URL: https://www.gov; Unique identifier: NCT04198701.
Updates to Table 1, the Institutional Review Board Statement, the Additional Information Section, and References
Authors: Håkon Vegrim, Torbjörn Tomson, Marte-Helene Bjørk
Journal: JAMA Neurology (2023)

Cameron Miller-Patterson, MD, MS; Jesse Y. Hsu, PhD, MS; Allison W. Willis, MD, MS; Ali G. Hamedani, MD, MHS
Association Between State Antibullying Policies and Suicidal Behaviors Among Lesbian, Gay, Bisexual, and Questioning Youth
Authors: Yang Liang, Daniel I. Rees, Joseph J. Sabia, Cooper Smiley
Journal: JAMA Pediatrics (2023)

This case-control study uses data from the 2009-2017 Youth Risk Behavior Survey to explore the association between antibullying law adoption and changes in suicidal behaviors among lesbian, gay, bisexual, and questioning youth.
Bringing Prostate Cancer Polygenic Risk Scores to the Clinic
Authors: Robert J. Klein
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Recall of Philips Respironics Ventilators and CPAP Machines—Breakdowns in Medical Device Surveillance
Authors: Robert A. Lowe
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Disruption of Phosphodiesterase 3A Binding to SERCA2 Increases SERCA2 Activity and Reduces Mortality in Mice With Chronic Heart Failure
Authors: Jonas Skogestad, Ingrid Albert, Karina Hougen, Gustav B. Lothe, Marianne Lunde, Olav Søvik Eken, Ioanni Veras, Ngoc Trang Thi Huynh, Mira Børstad, Serena Marshall, Xin Shen, William E. Louch, Emma Louise Robinson, Joseph C. Cleveland, Amrut V. Ambardekar, Jessica A. Schwisow, Eric Jonas, Ana I. Calejo, Jens Preben Morth, Kjetil Taskén, Arne Olav Melleby, Per Kristian Lunde, Ivar Sjaastad, Cathrine Rein Carlson, Jan Magnus Aronsen
Journal: Circulation (2023)

Increasing SERCA2 (sarco[endo]-plasmic reticulum Ca2+ ATPase 2) activity is suggested to be beneficial in chronic heart failure, but no selective SERCA2-activating drugs are available. PDE3A (phosphodiesterase 3A) is proposed to be present in the SERCA2 interactome and limit SERCA2 activity. Disruption of PDE3A from SERCA2 might thus be a strategy to develop SERCA2 activators.Confocal microscopy, 2-color direct stochastic optical reconstruction microscopy, proximity ligation assays, immunoprecipitations, peptide arrays, and surface plasmon resonance were used to investigate colocalization between SERCA2 and PDE3A in cardiomyocytes, map the SERCA2/PDE3A interaction sites, and optimize disruptor peptides that release PDE3A from SERCA2. Functional experiments assessing the effect of PDE3A-binding to SERCA2 were performed in cardiomyocytes and HEK293 vesicles. The effect of SERCA2/PDE3A disruption by the disruptor peptide OptF (optimized peptide F) on cardiac mortality and function was evaluated during 20 weeks in 2 consecutive randomized, blinded, and controlled preclinical trials in a total of 148 mice injected with recombinant adeno-associated virus 9 (rAAV9)-OptF, rAAV9-control (Ctrl), or PBS, before undergoing aortic banding (AB) or sham surgery and subsequent phenotyping with serial echocardiography, cardiac magnetic resonance imaging, histology, and functional and molecular assays.PDE3A colocalized with SERCA2 in human nonfailing, human failing, and rodent myocardium. Amino acids 277-402 of PDE3A bound directly to amino acids 169-216 within the actuator domain of SERCA2. Disruption of PDE3A from SERCA2 increased SERCA2 activity in normal and failing cardiomyocytes. SERCA2/PDE3A disruptor peptides increased SERCA2 activity also in the presence of protein kinase A inhibitors and in phospholamban-deficient mice, and had no effect in mice with cardiomyocyte-specific inactivation of SERCA2. Cotransfection of PDE3A reduced SERCA2 activity in HEK293 vesicles. Treatment with rAAV9-OptF reduced cardiac mortality compared with rAAV9-Ctrl (hazard ratio, 0.26 [95% CI, 0.11 to 0.63]) and PBS (hazard ratio, 0.28 [95% CI, 0.09 to 0.90]) 20 weeks after AB. Mice injected with rAAV9-OptF had improved contractility and no difference in cardiac remodeling compared with rAAV9-Ctrl after aortic banding.Our results suggest that PDE3A regulates SERCA2 activity through direct binding, independently of the catalytic activity of PDE3A. Targeting the SERCA2/PDE3A interaction prevented cardiac mortality after AB, most likely by improving cardiac contractility.